132 Immunity 



of great simplicity. The governmental laboratory furnishes the 

 "test toxin" whose strength is guaranteed, and what follows is a 

 simple matter of dilution, admixture with the serum to be tested, 

 and the injection of animals that are carefully observed for a few 

 days. 



The entire subject, historical, theoretical, and practical, is treated 

 in Bulletin No. 43, 1908, of the Hygienic Laboratory upon "The 

 Standardization of Tetanus Antitoxin," by Rosenau and Anderson. 



Antivenene or Anti-venomous Serum.— This was discovered 

 by Phisalix and Bertrand* and made practical for therapeutic 

 purposes by Calmette.f Calmette found that cobra venom con- 

 tained two principles, one of which, labile in nature and readily 

 destroyed by heat, was destructive in action upon the tissues with 

 which it came into direct contact; the other, stable in nature, was 

 death-dealing through its action upon the respiratory centers. By 

 heating the venoms and thus destroying the irritative principle, 

 he was able to immunize animals against the other, which he looked 

 upon as the important element of the venom. The immunized 

 animals furnished an anti-serum, which entirely annulled the effect 

 of the toxin (modified venom) used in treating them. This serum 

 was found to protect rabbits and other animals against both modi- 

 fied and unmodified cobra venom, and was used successfully in 

 the treatment of a number of human beings who had been bitten 

 by cobras. Calmette, however, erroneously concluded that be- 

 cause in most venoms studied he was able to find a larger or smaller 

 proportion of the respiratory poison, it constituted the essential 

 element of the venom to be antagonized. Arguing from this stand- 

 point, he recommended his antivenene in all cases of snake-bite, 

 regardless of the variety of serpent. C. J. Martint and others 

 showed that Calmette was wrong, and that his antivenene was 

 useless in the treatment of the bites of the Australian serpents, 

 and the experiments of the author have shown it to be useless in the 

 treatment of the bites of the American snakes. In the venoms of our 

 snakes — the rattlesnake, copper-head, and moccasin — the poison 

 is essentially locally destructive in action, the fatal influence upon 

 the respiratory centers being of secondary importance. Flexnerand 

 Noguchi,§ Noguchi|| and Madsen and Noguchi,** however, ap- 

 plied Ehrlich's principle to the investigation, destroyed the toxo- 

 phorous group of the venom molecules, and succeeded in producing 

 an anti-serum useful in antagonizing the active principle — hemor- 

 rhagin — -of the Crotalus venom. 



*"Compt. rendu de I'Acad. des Sciences de Paris," Feb. 5, 1894, cxviii, 

 P- 356. 



t "Compt. rendu de la Soc. de Biol, de Paris," Feb. 10, 1894, 10 Series, i, 

 p. 120. 



% "Intercolonial Medical Journal of Australia," 1897, 11, p. 537. 



§ "Journal of Experimental Medicine," 1901-1905, vi, p. 277. 



II Ibid., 1906, vin, p. 614. 

 **Ibid., 1907, IX, p. 18. 



